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在大鼠中使用光纤共聚焦荧光显微镜进行胰腺癌分期的可行性和可靠性。

Feasibility and reliability of pancreatic cancer staging using fiberoptic confocal fluorescence microscopy in rats.

作者信息

Ignat Mihaela, Aprahamian Marc, Lindner Veronique, Altmeyer Anaïs, Perretta Silvana, Dallemagne Bernard, Mutter Didier, Marescaux Jacques

机构信息

IRCAD, Strasbourg, France.

出版信息

Gastroenterology. 2009 Nov;137(5):1584-92.e1. doi: 10.1053/j.gastro.2009.07.045. Epub 2009 Jul 24.

Abstract

BACKGROUND & AIMS: Surgical management of pancreatic cancer depends on tumor resectability and staging. This study evaluated a new in vivo technique, fiberoptic confocal fluorescence microscopy (FCFM), for detection and staging of pancreatic tumors in rats.

METHODS

FCFM was used with a protease-activated fluorescent marker (ProSense; VisEn Medical Inc, Woburn, MA) for in vivo imaging of solid organs (1.8-microm resolution) in a rat model of pancreatic ductal adenocarcinoma. A preliminary study described the FCFM rendering of normal and pathologic tissues. Subsequently, 2 double-blind studies compared FCFM to standard histology in (1) detection of tumors in rat models of cancer and controls and (2) detection of nodal involvement (splenic, celiac, mesenteric, and colic) 4, 5, and 6 weeks after tumor induction vs controls.

RESULTS

Tumor cells displayed a fluorescent ductal pattern compared with non-fluorescent normal pancreas or normal follicular pattern of lymph nodes (LNs). FCFM detected all the pancreatic tumors (1.7-mm mean diameter) and identified 23 LNs that contained metastases of 99 LNs examined. Standard histologic analyses resulted in 1 false-negative result in tumor detection and 2 false negatives in LN detection, whereas FCFM produced no false-negative results. Additional serial sectioning confirmed all tumors and 16 metastatic LNs; FCFM had a negative predictive value of 100% and a positive predictive value of 69.6%.

CONCLUSIONS

Real-time "virtual biopsy" using FCFM detects tumors and LN metastases with 100% sensitivity and 92.2% specificity in rats, making it a reliable technique for detection and staging of pancreatic cancer.

摘要

背景与目的

胰腺癌的手术治疗取决于肿瘤的可切除性和分期。本研究评估了一种新的体内技术——光纤共聚焦荧光显微镜(FCFM),用于大鼠胰腺肿瘤的检测和分期。

方法

在胰腺导管腺癌大鼠模型中,使用FCFM和蛋白酶激活荧光标记物(ProSense;VisEn Medical Inc,沃本,马萨诸塞州)对实体器官进行体内成像(分辨率为1.8微米)。一项初步研究描述了FCFM对正常和病理组织的成像情况。随后,进行了两项双盲研究,将FCFM与标准组织学方法在以下两方面进行比较:(1)在癌症大鼠模型和对照组中检测肿瘤;(2)在肿瘤诱导后4、5和6周与对照组比较,检测淋巴结受累情况(脾、腹腔、肠系膜和结肠淋巴结)。

结果

与非荧光的正常胰腺或正常淋巴结滤泡模式相比,肿瘤细胞呈现荧光导管模式。FCFM检测到了所有胰腺肿瘤(平均直径1.7毫米),并在检查的99个淋巴结中识别出23个有转移的淋巴结。标准组织学分析在肿瘤检测中有1例假阴性结果,在淋巴结检测中有2例假阴性结果,而FCFM没有产生假阴性结果。额外的连续切片证实了所有肿瘤和16个转移淋巴结;FCFM的阴性预测值为100%,阳性预测值为69.6%。

结论

使用FCFM进行实时“虚拟活检”在大鼠中检测肿瘤和淋巴结转移的灵敏度为100%,特异性为92.2%,使其成为一种可靠的胰腺癌检测和分期技术。

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